Regulation of cytokinesis
Regulation of cytokinesis
批准号:
9928170
负责人:
Kathleen L Gould
金额:
$15.07万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-05-01 至 2024-04-30
关键词:
ActinsAnimal ModelArchitectureCSNK1A1 geneCell CycleCell DeathCell PolarityCell divisionCell membraneCellsChromosome SegregationComplementCytokinesisDefectDevelopmentEnsureEnzymesEventFamilyFission YeastGenetic ScreeningGenomic InstabilityGoalsHomeostasisHumanKnowledgeLearningLocationMaintenanceMicroscopyMitosisMitotic CheckpointMitotic spindleMolecular StructureMyosin ATPasePathway interactionsPhosphotransferasesProcessProteinsProteomicsRegulationResearchRoleSignal TransductionStressTestingTimeTissuesWorkYeastsbasechromosome replicationdaughter celldesignevent cyclehuman diseaseinterdisciplinary approachphysical separationpreventscaffold
中文摘要
摘要
胞质分裂,即一个细胞分裂成两个子细胞的物理分离,是细胞分裂的最后阶段,
尽管人们对它知之甚少,但它是发育和组织动态平衡的核心。正确计时
胞质分裂,使其仅在染色体复制和分离后发生,以防止
灾难性的基因组不稳定,因此,细胞质分裂与其他细胞周期相一致地受到严格调控
事件。使用一种强大的模式生物,裂殖酵母裂殖酵母庞贝,我的实验室已经
进行了开创性的研究,以确定细胞质分裂所必需的蛋白质,并了解无数
组成细胞分裂机制的蛋白质被协调以确保精致的空间和时间
控制细胞分裂。我们建议继续我们在这一领域的基本问题的工作,使用
在两个方向上采取多学科方法。在一个方向上,我们将解决胞质分裂是如何伴随着
通过研究当有丝分裂纺锤体时导致胞质分裂抑制的缺陷来研究有丝分裂的其他事件
被破坏,调节有丝分裂检查点的这一分支的CK1酶如何被纺锤体激活
应激,以及CK1信号如何在纺锤体极点与其他途径整合。了解CK1
有丝分裂检查点方面的监管也将为此建立一般的监管机制
酶家族,它们是保守的、多功能的激酶,在许多人类疾病中发挥作用。在一个
第二个方向,我们将加深对收缩环的组装和结构的理解
使用复杂的显微镜方法。我们将继续积累我们对
收缩环,F-bar蛋白CDC15,通过定义它如何在质膜上齐聚,以及
其他收缩环部件在CDC15支架上是如何组织的。我们还将检验我们的假设
多个细胞周期和极性激酶在不适当的情况下抑制了CDC15支架的建立
地点和时间,确保它在有丝分裂过程中只在细胞中部组装。这些专注的机械论
研究将得到蛋白质组学和大规模基因筛查的补充,旨在建立
收缩环部件的功能相互作用网络。总而言之,这些研究将产生重大影响
以了解细胞质分裂是如何在从酵母到人类的真核物种中协调进行的。
英文摘要
Abstract
Cytokinesis, the physical separation of one cell into two daughter cells, is the final stage of cell division, and
although it is the least well understood, it is central to development and tissue homeostasis. Correctly timing
cytokinesis so that it occurs only after chromosome replication and segregation is necessary to prevent
catastrophic genomic instability, and accordingly, cytokinesis is strictly regulated in concert with other cell cycle
events. Using a powerful model organism, the fission yeast Schizosaccharomyces pombe, my lab has
conducted pioneering research to identify proteins essential for cytokinesis and to learn how the myriad
proteins that comprise the cell division machinery are coordinated to ensure the exquisite spatial and temporal
control of cell division. We propose to continue our work pursuing fundamental questions in this field using a
multi-disciplinary approach in two directions. In one direction, we will tackle how cytokinesis is entrained with
other events of mitosis by investigating the defect that leads to inhibition of cytokinesis when the mitotic spindle
is disrupted, how the CK1 enzymes that regulate this branch of the mitotic checkpoint are activated by spindle
stress, and how CK1 signalling is integrated with other pathways at spindle poles. Understanding CK1
regulation in the context of the mitotic checkpoint will also establish general mechanisms of regulation for this
enzyme family, which are conserved, multifunctional kinases with roles in numerous human diseases. In a
second direction, we will advance our understanding of the assembly and architecture of the contractile ring
using sophisticated microscopy approaches. We will continue to build our knowledge of the major scaffold of
the contractile ring, the F-BAR protein Cdc15, by defining how it oligomerizes on the plasma membrane, and
how other contractile ring components are organized on the Cdc15 scaffold. We will also test our hypothesis
that multiple cell cycle and polarity kinases inhibit the establishment of the Cdc15 scaffold at inappropriate
locations and times, ensuring it only assembles in the cell middle during mitosis. These focused mechanistic
studies will be complemented with proteomic and large-scale genetic screens designed to establish a
functional interaction network of contractile ring components. Together, these studies will have a major impact
for understanding how cytokinesis is orchestrated in eukaryotic species from yeast to humans.
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会议论文
Regulation of cytokinesis
-
批准号:10152616
-
项目类别:
-
资助金额:$69.7万
-
财政年份:2019
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
-
批准号:10800229
-
项目类别:
-
资助金额:$1.51万
-
财政年份:2019
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
-
批准号:9921422
-
项目类别:
-
资助金额:$69.7万
-
财政年份:2019
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
-
批准号:10613993
-
项目类别:
-
资助金额:$69.7万
-
财政年份:2019
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
-
批准号:10794021
-
项目类别:
-
资助金额:$22.98万
-
财政年份:2019
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
-
批准号:10392903
-
项目类别:
-
资助金额:$69.7万
-
财政年份:2019
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
-
批准号:10380944
-
项目类别:
-
资助金额:$8.78万
-
财政年份:2019
-
负责人:Kathleen L Gould
-
依托单位:
Checkpoint control of cytokinesis
-
批准号:8799120
-
项目类别:
-
资助金额:$37.62万
-
财政年份:2014
-
负责人:Kathleen L Gould
-
依托单位:
FASEB SRC on Yeast Chromosome Structure, Replication and Segregation
-
批准号:8781775
-
项目类别:
-
资助金额:$0.8万
-
财政年份:2014
-
负责人:Kathleen L Gould
-
依托单位:
Checkpoint control of cytokinesis
-
批准号:9111001
-
项目类别:
-
资助金额:$37.62万
-
财政年份:2014
-
负责人:Kathleen L Gould
-
依托单位:
Checkpoint control of cytokinesis
-
批准号:9321309
-
项目类别:
-
资助金额:$37.62万
-
财政年份:2014
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
-
批准号:8899297
-
项目类别:
-
资助金额:$4.45万
-
财政年份:2012
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负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
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批准号:8271883
-
项目类别:
-
资助金额:$28.52万
-
财政年份:2012
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
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批准号:8471733
-
项目类别:
-
资助金额:$28.37万
-
财政年份:2012
-
负责人:Kathleen L Gould
-
依托单位:
Regulation of cytokinesis
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批准号:8642655
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项目类别:
-
资助金额:$29.39万
-
财政年份:2012
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负责人:Kathleen L Gould
-
依托单位:
ANALYSIS OF S POMBE CDC15 PHOSPHORYLATION AND INTERACTION PARTNERS
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批准号:8365903
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项目类别:
-
资助金额:$0.74万
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财政年份:2011
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负责人:Kathleen L Gould
-
依托单位:
SYSTEMATIC TWO-HYBRID AND COMPARATIVE PROTEOMIC ANALYSES
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批准号:8365862
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项目类别:
-
资助金额:$2.18万
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财政年份:2011
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负责人:Kathleen L Gould
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依托单位:
FRET ANALYSIS OF FISSION YEAST SPB COMPONENTS
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批准号:7957792
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项目类别:
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资助金额:$1.63万
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财政年份:2009
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负责人:Kathleen L Gould
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依托单位:
CHARACTERIZATION OF PLO1P INTERACTORS AND PHOSPHORYLATION SITES
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批准号:7723645
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项目类别:
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资助金额:$0.08万
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财政年份:2008
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负责人:Kathleen L Gould
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依托单位:
IDENTIFICATION OF CLP1P INTERACTING PROTEINS
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批准号:7602227
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项目类别:
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资助金额:$0.08万
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财政年份:2007
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负责人:Kathleen L Gould
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依托单位:
海外基金